Fig. 6.8D ), the summation becomes less than linear because of what is known as a shunting effect. That is, when synapse 2 is active, channels are opened in the cell membrane, which means that it is more leaky. Therefore, when synapse 4 is also active, more of its EPSC will be lost (shunted) through the dendritic membrane, and less current will be left to travel down the dendrite to the initial segment. The result is that synapse 4 causes a smaller EPSP at the initial segment than it would have generated in isolation. Nevertheless, the combined EPSP is still larger than an EPSP caused by either synapse 2 or 4 alone.
Where do IPSPs fit into synaptic integration? In many cases one can think of them as negative EPSPs. Thus, whereas EPSPs add together to help bring the membrane potential up to and beyond the spiking threshold, IPSPs subtract from the membrane potential to make it more negative and therefore further from threshold. In deciding whether to spike, a cell adds up the ongoing EPSPs and subtracts the IPSPS to determine whether the sum reaches threshold. As with an EPSP, the efficacy of an IPSP varies with its location.
In addition to subtracting algebraically from the membrane potential, IPSPs exert an inhibitory action via the shunting mechanism, just as was described earlier for EPSPs. That is, while the IPSP channels are open, they make the membrane more leaky (i.e., lower its resistance) and thereby reduce the size of EPSPs, thus making them less effective. This shunting mechanism explains how IPSPs that do not change the membrane potential—or even those that slightly depolarize it—can still decrease the excitability of the cell. An alternative way to look at this effect is to view each synapse as a device that tries to bring the membrane potential to its own equilibrium potential. Because this potential is below the action potential threshold in the case of IPSPs, IPSPs make it harder for the cell to spike.
Thus far the interaction of synaptic potentials has been presented under the assumption that the postsynaptic cell membrane is passive (i.e., it acts as though it were simply resistors and capacitors in parallel with each other). However, it is clear that the dendrites and somas of most, if not all, neurons contain active elements (i.e., gated channels) that can amplify and alter EPSPs and IPSPs. For example, a distal EPSP can have a larger-than-expected effect if the EPSP activates dendritically-located voltage-gated Na+ or Ca++ channels that boost its amplitude or even generate propagated dendritic action potentials. Another example is Ca++-activated K+ channels that are present in the dendrites of some neurons. These channels are activated by the influx of Ca++ either through synaptic channels or via dendritic voltage-gated Ca++ channels opened by EPSPs and can cause long-lasting hyperpolarizations that effectively make the cell inexcitable for tens to hundreds of milliseconds. As a final example, there are some Ca++ channels that underlie a low-threshold Ca++ spike. These channels are normally inactive at resting membrane potentials, but the hyperpolarization that results from a large IPSP can de-inactivate them and allow them to open (and produce a spike) after termination of the IPSP. In this case “inhibition” actually increases the cell’s excitability. In sum, synaptic integration is a highly complex, nonlinear process. Nevertheless, the basic principles just described remain at its core.
Modulation of Synaptic Activity
Integration of synaptic input by a postsynaptic neuron, as described in the previous section, represents one aspect of the dynamic nature of synaptic transmission. A second aspect is that the strength of individual synapses can vary as a function of their use or activity. That is, a synapse’s current functional state reflects, to some extent, its history.